Esophageal cancer is a deadly disease with limited treatment options. In addition to modest effects, toxic chemo-therapy drugs cripple patients with debilitating side-effects. This proposal utilizes an Esophageal Theranostic Delivery System (ETDS), to address this clinical need with a multi-modal solution. It delivers a theranostic combination of chemotherapy drugs and a fluorescent dye directly to the cancer. The combination is loaded on a nano-porous, tantalum surface on the ETDS. The physical scaffold props open any obstruction, the combination drugs treat the cancer, and the fluorescent dye lights up the tumor, allowing monitoring of the treatment. The ETDS is predicted to provide acute relief in patients suffering from dysphagia (difficulty swallowing), enhance therapeutic effectiveness, reduce systemic toxicity, and improve quality of life. More importantly, in combination with other therapies, it has the potential to prolong life. It is a platform technology and has the potential to treat other cancers. The long-term objective is to develop a loco-regional ETDS to treat esophageal cancer as an adjunct to systemic therapy. The specific aims of this proposal include: demonstrating the feasibility of developing a prototype ETDS with slow, medium and fast drug and dye release profiles;developing methodologies to test performance of the formulations;demonstrating proof-of-concept efficacy in a mouse model;and comparing the drug exposure in the tumor model at the efficacious ETDS dose to a systemic dose. The research methods are expected to result in: prototypes of ETDS that can be engineered to release drugs at the desired rate;identification of a therapeutically effective dose in the mouse tumor model;a product profile to support clinical testing.